Seminar – MPFI Seminar Series

Human-specific modifiers of synaptic development, cortical circuit connectivity and function

Franck Polleux

Jan 23,
  • Time:
  • Location: MPFI - Elmore Auditorium
  • Host: Hiroki Taniguchi
  • Speaker: Franck Polleux

The remarkable cognitive abilities characterizing humans has been linked to unique patterns of connectivity characterizing the neocortex. Comparative studies have shown that human cortical pyramidal neurons (PN) receive a significant increase of synaptic inputs when compared to other mammals, including non-human primates and rodents, but how this may relate to changes in cortical connectivity and function remains largely unknown. We previously identified a human-specific gene duplication (HSGD), SRGAP2C, that, when induced in mouse cortical PNs drives human-specific features of synaptic development, including a correlated increase in excitatory (E) and inhibitory (I) synapse density (Charrier et al. Cell 2012; Fossatti et al. Neuron 2016). However, the origin and nature of this increased connectivity and its impact on cortical circuit function was unknown. Here, using a combination of transgenic approaches and quantitative monosynaptic tracing, we demonstrate that humanization of SRGAP2C expression in the mouse cortex leads to a specific increase in local and long-range cortico-cortical inputs received by layer 2/3 cortical PNs. Moreover, using in vivo 2-photon imaging in the barrel cortex of awake mice, we show that humanization of SRGAP2C expression increases the reliability and selectivity of sensory-evoked responses in layer 2/3 PNs. Our results suggest that the emergence of SRGAP2C during human evolution led to increased local and long-range cortico-cortical connectivity and improved reliability of sensory-evoked cortical coding.